A double-blinded, randomized, controlled trial was carried out in in Melbourne, Australia, to determine the contribution of drinking water to gastroenteritis. Melbourne is one of the few major cities in the world that draws drinking water from a protected forest catchment with minimal water treatment (chlorination only). Six hundred families were randomly allocated to receive either real or sham water treatment units (WTUs) installed in their kitchen. Real units were designed to remove viruses, bacteria, and protozoa. Study participants completed a weekly health diary reporting gastrointestinal symptoms during the 68-week observation period. There were 2,669 cases of highly credible gastroenteritis (HCG) during the study (0.80 cases/person/year). The ratio of HCG episode rates for the real WTU group compared to the sham WTU group was 0.99 (95% confidence interval, 0.85-1.15, p = 0.85). We collected 795 fecal specimens from participants with gastroenteritis, and pathogens were not more significantly common in the sham WTU group. We found no evidence of waterborne disease in Melbourne. The application of this methodology to other water supplies will provide a better understanding of the relationship between human health and water quality.